Effect of Zinc Ions on the Proliferation and Differentiation of Keratinocytes

Abstract

Background: Psoriasis is a chronic inflammatory disease in which there is hyperproliferation and abnormal differentiation of keratinocytes. Since high levels of KLK7, an enzyme inhibited by zinc (Zn2+) ions, are present in psoriatic lesions, we have studied the effect of zinc ions in the viability of keratinocytes, as well as in the activity of KLK5 and KLK7 and in the expression of epidermal markers. Methods and Results: The cells were cultured in the absence or presence of Zn2+ ions (5.0, 10 and 25 M). Cell viability was evaluated by the MTT method after during 14 days. Cell death was evaluated by flow cytometry using propidium iodide. The activity of the KLK was evaluated on the hydrolysis of synthetic substrates. Expression of involucrin, filaggrin, cytokeratins (CK) 5, 10 and 14 was evaluated by quantitative PCR. Cell incubation with Zn2+ ions did not result in significant changes in cell viability. By MTT assay, it was observed that the cultures incubated with 10 and 25 M Zn2+ ions showed a decrease in the number of viable cells in comparison to the control. Cells cultured for 1 day in the presence of 25 M Zn2+ ions displayed a decrease in KLK7 activity. In the presence of Zn2+ ions, it was shown an increase in the expression of CK5, 10 and 14, involucrin and filaggrin. Conclusions: These results have shown that zinc ions can affect the differentiation of HaCat cells, contributing for future therapeutic trials related to psoriasis based on the modulation of KLK activity.